Mitochondrial Omics in Macrophage Foam Cell Formation and Atherosclerosis.

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death worldwide, with atherosclerosis serving as the core pathological mechanism driving ischemic heart disease, ischemic stroke, and peripheral artery disease. Macrophages play a central role in atherosclerosis by internalizing modified lipids and transforming them into foam cells, thereby driving plaque formation and progression. Mitochondrial metabolism is critically involved in regulating macrophage function, and targeting mitochondrial dysfunction may provide strategies for limiting plaque inflammation and improving plaque stability. Advances in high-throughput omics technologies and bioinformatic analysis methods have provided powerful tools for in-depth investigation of mitochondrial function. This review first summarizes macrophage heterogeneity and foam cell formation in atherosclerotic plaques. It then compares mitochondrial omics approaches, including proteomics, interactomics, metabolomics, lipidomics, isotope tracing, and emerging single-cell and spatial omics strategies. Finally, it discusses how mitochondrial dysfunction and metabolic reprogramming contribute to macrophage foam cell formation, plaque inflammation, and atherosclerosis progression.